title: Studies on agents with vasodilator and beta-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665.
abstract: Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether. (3). The hypotensive and beta-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, Ra,Sb-one (1c) possessed the essential activities of TZC-5665 (1).
authors.affiliation: Research Division, Teikoku Hormone Manufacturing Co., Ltd., Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Seki
authors.forename: A
authors.initials: A
authors.lastname: Kanada
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Shiraiwa
authors.forename: H
authors.initials: H
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Miyazawa
authors.forename: T
authors.initials: T
authors.lastname: Ishimori
authors.forename: N
authors.initials: N
authors.lastname: Minami
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000737:chemistry; D006333:Heart Failure / Q000188:drug therapy; D007275:Injections, Intravenous; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D011724:Pyridazines; D014665:Vasodilator Agents; C020344:glycidyl ethers; C088090:TZC 5665; D015105:3',5'-Cyclic-AMP Phosphodiesterases